• Open Access

Efficient 18F-Labeling of Synthetic Exendin-4 Analogues for Imaging Beta Cells

Authors

  • Dr.  Edmund J. Keliher,

    1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 (USA), Fax: (+1) 617-726-8226
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    • These authors contributed equally

  • Dr.  Thomas Reiner,

    1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 (USA), Fax: (+1) 617-726-8226
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    • These authors contributed equally

  • Dr.  Greg M. Thurber,

    1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 (USA), Fax: (+1) 617-726-8226
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  • Rabi Upadhyay,

    1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 (USA), Fax: (+1) 617-726-8226
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  • Prof.  Ralph Weissleder

    Corresponding author
    1. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 (USA), Fax: (+1) 617-726-8226
    2. Department of Systems Biology, Harvard Medical School, 200 Longwood Ave, Boston, MA 02115 (USA)
    • Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge St, CPZN 5206, Boston, MA 02114 (USA), Fax: (+1) 617-726-8226
    Search for more papers by this author

Abstract

A number of exendin derivatives have been developed to target glucagon-like peptide 1 (GLP-1) receptors on beta cells in vivo. Modifications of exendin analogues have been shown to have significant effects on pharmacokinetics and, as such, have been used to develop a variety of therapeutic compounds. Here, we show that an exendin-4, modified at position 12 with a cysteine conjugated to a tetrazine, can be labeled with 18F-trans-cyclooctene and converted into a PET imaging agent at high yields and with good selectivity. The agent accumulates in beta cells in vivo and has sufficiently high accumulation in mouse models of insulinomas to enable in vivo imaging.

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